JP2919971B2 - Method for coating a pharmaceutical tablet core with a coating material and apparatus for performing the method - Google Patents

Abstract

A method of coating substrates of medicinal products with a dry powder includes the following steps: feeding the medicinal substrates onto a conveying belt (1); supplying the dry powder to a region (5) through which the substrates are to be conveyed; conveying the medicinal substrates on the conveying belt (1) through the region (5) with the conveying belt and/or the substrates maintained at a different electric potential from the dry powder, whereby the dry powder is attracted to the exposed surfaces of the substrates but is unable to reach the coated surfaces of the substrates in contact with the conveying belt, and treating the dry powder coatings to convert the powder into a fused film secured to the substrates.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method of coating a pharmaceutical tablet core with a coating material and an apparatus for performing the method.

At least the suggestions for electrostatic coating of tablets,
It has been around for about 30 years. For example, British Patent Specification GB-1075404 (published 1967) states that when a tablet core is conveyed below a first stage sprayer with an integrated high pressure grid, a liquid is sprayed on one side of each tablet and the coating is dried. The coated core was then transported down the second stage sprayer with an integrated high pressure grid, with the coated core carried the other side of the tablet up, and then the coating was dried again. An apparatus has been proposed.

Various papers have been proposed to electrostatically coat tablet cores using liquids or dry powders, but at least for pharmaceutical tablets, electrostatics have proven to be sufficiently successful for commercial application on a reasonable scale. No coating method or apparatus has been recognized so far. For example, there are rotary tablet presses that can continuously produce pharmaceutical tablet cores at a rate of 5000 tablets per minute, but the next tablet core coating is most commonly used as a batch process by applying a liquid coating in a rotating drum. Done in

Various problems must be overcome in order to obtain a commercially viable device or method for coating pharmaceuticals. Using a liquid as a coating material is easier than a dry powder in many respects, and studies have considered both options, but workers agree with the use of a liquid. If a dry powder is used, it is more difficult to obtain the adhesion of the coating to the substrate, and even if the powder is charged electrostatically, it is believed that it conducts electricity by itself. Absent. In order to provide a permanent bond between the substrate and the powder, the powder must be converted to a film, for example, by melting, but in the case of pharmaceuticals, which often include organic substances, must be damaged. No. Furthermore, even coatings are required, but even when the powders are charged electrostatically, it is very difficult to obtain a uniform coating of the powder on an electrically insulating pharmaceutical substrate.

If a liquid coating is used, the coating must be dried. Theoretically, in some circumstances, this type of drying can be performed at room temperature, but it is important in commercial practice, for example, because of the rate at which the process should be performed to heat the tablet. It is also expensive because of the large input of energy required to evaporate the solvent used in the liquid coating.
Another disadvantage of liquid coatings is that they cannot be used to coat materials that cannot be dissolved or properly dispersed in a usable liquid, desirably water.

SUMMARY OF THE INVENTION It is an object of the present invention to provide an improved method and apparatus for coating a pharmaceutical tablet core (herein "core" is also referred to as "substrate").

According to the present invention, a step of feeding a pharmaceutical tablet core onto a transport device; a step of supplying a coating material to an area where the core passes when transported on the transport device; Transporting the core through the region on the transport device while maintaining the potential at a different electrical potential, thereby attracting the coating material to an exposed surface of the core to form a coating on the exposed surface. A method of coating a coating material on a pharmaceutical tablet core comprising: using a dry powder as the coating material, wherein the dry powder is attracted to an exposed surface of the core to form a coating on the exposed surface. Later treating the dry powder so as to convert it to a fused film coating adhered to the core. Is provided.

It has been found that placing the substrate on a transport device during the charging process can result in good spreading of the powder on the substrate. Also, although having a coating of nearly constant thickness is important for the final tablet,
It has also been found that some unevenness in the distribution is not necessarily critical, as further leveling can occur if the powder is converted to a fused film. Thus, the present invention allows a coating of a desired thickness to be evenly applied on the surface of a substrate. Coating thickness is generally 10
It is larger than μm. The invention as defined above further comprises:
It requires the input of energy to convert the powder into a fused film, but the amount of energy required is to apply a liquid coating containing the coating material dissolved in a suitable solvent and to evaporate the solvent after the application of the coating. It may be significantly less than that required when it must. This method eliminates the need for solvent processing and disposal, as well as batch operations.

The pharmaceuticals are usually pharmaceutical tablets ("tablets" are defined below), but they may also be implants that are not administered orally. Reference is made throughout the specification to "tablets" and the invention is of particular application to pharmaceutical tablets of conventional shape, but the term is broadly defined to include, for example, pellets, capsules or spheroids. It should be understood that

The method of the present invention is generally used to coat tablet cores (or pharmaceutical substrates) that have not been subjected to any coating since they were formed in a press, but over coated or partially coated tablet cores. It can also be used to apply a coating to a coating.

The method of the present invention can also be performed as a continuous process. In fact, it is a considerable advantage that the coating process can be operated continuously rather than as a batch process. It is desirable to coat the pharmaceutical substrate on one side only or with at least one discontinuity in the coating, although there are some applications mentioned below, but generally coating all of the outer surface of the tablet core Is desirable. Therefore, this method preferably
Exposing the surface of the core that has been in contact with the transfer device in the transfer step and contacting the fused film coating of the core with the transfer device to feed a tablet core onto the transfer device; Supplying the dry powder to be coated on the core to an area through which the transport device passes, and maintaining the transport device and / or the core, or both at a different potential from the dry powder, and moving the core through the area. And transported on said transport device, thereby
Allowing the dry powder to be attracted to the exposed surface of the core; and treating the dry powder coating to convert the newly attracted powder to a fused film coating affixed to the core. Are included as further subsequent steps.

For practical convenience, it is preferred that the transport device used during the second coating stage is not the one used during the first coating stage, but it is possible to use the same transport device for both coating stages. The powder applied during each coating stage is usually the same, but it goes without saying that it is possible to apply a different powder to each stage, as well as usually the same coating thickness at each stage However, various thicknesses can be applied if desired.

If desired, further coating steps can be used, for example, to apply powders to the sides of the medicament if they are uncoated.

Preferably, the transport device comprises a conveyor belt. However, the transport device may include an inclined stationary or vibrating surface along which the substrate slides. Friction between the substrate and the ramp can be reduced by passing air from the back side to the ramp.

The step of converting the powder into a fused film is conveniently
After the powder has been converted to the liquid phase, it can include the step of returning to the solid phase.

Applicants have reported that the conversion of the dry powder to a fused film
It has been found that not only does it help to adhere the coating to the substrate, but it also provides an apparatus that allows a more even distribution of the coating material on the substrate.
In some cases, when melted, the coating material has a viscosity low enough to distribute the coating itself to the substrate evenly, but in many cases, the coating material is more viscous, and thus, Preferably
Still other mechanical treatments of the coating are included to equalize the depth of the coating on the surface of the substrate. The equalization step can be performed by passing the substrate under a vibrating plate or rotating roller, which contacts or equalizes the coating on the substrate. Alternatively, the equalization step
This can be done by passing the substrate under a jet of air, e.g. an air knife, where an air curtain created as an air knife equalizes the coating on the substrate, but avoids premature solidification of the coating. The air can also be heated.

The dry powder is preferably converted to a fused film, preferably by heating with infrared radiation, although other types of electromagnetic radiation may be used. Conversion to a fused film can also be achieved to some extent or all by reducing the pressure in that area. Usually, the change in coating is merely a physical change from a powder to a liquid on heating and then a continuous solid coating on cooling, but there are other possibilities as well, for example, where a powder coating is It may also include a polymer that is cured during the process step by irradiation with energy, for example, gamma, ultraviolet or radio frequency bands, to form a coating of a continuously crosslinked polymer.

It is desirable to charge the powder to an appropriate potential, which can be positive or negative. Desirably, the powder is charged as it is supplied to the area through which the transport device passes. Charging can also be performed using a corona charging device, but another possibility is to triboelectrically charge the powder. Usually, one or more pairs of electrodes maintained at a selected potential of the same sign as that of the powder (ie, a positive potential if the powder is positively charged, and a negative potential if the powder is negatively charged). However, desirably, it is provided in an area above the conveying device where the powder is supplied. The positioning of the electrodes and the potential or potentials at which they are maintained will affect the electric field in the region and thus the path of the powder through the region.

The transport device is desirably maintained at either ground potential or the potential opposite to that at which the powder is charged.
The delivery device may also have a conductive top surface on which the medicament substrate rests. In many cases, the substrates are made of an electrically insulating material, but they can also be treated prior to application of the powder to make them more conductive, for example by wetting the outer surface of the substrate. This type of humidification facilitates maintenance of the outer surface of the substrate at ground potential, and thus facilitates application of the powder to the core.

The method of the present invention is not limited to the use of any particular type of coating material. On the other hand, in order to obtain good results, it is desirable that the dry powder has the following physical properties.

(1) 1 μm to 1000 μm, preferably 30 μm
Particle size in the range from to 80 μm. The small particle size allows the powder to be fed and distributed evenly into the area where the conveyor belt passes.

(2) In the range of 10 ⁶ Ωm to 10 ²⁴ Ωm, preferably 10 ¹⁰ Ωm
Relatively high resistivity in the range Ωm to 10 ¹⁴ Ωm. High resistivity makes it easier to maintain the powder charge, but makes it more difficult to charge the powder.

(3) Less than 500 Pas, preferably in the liquid phase
Viscosity less than 75 Pas. The low viscosity facilitates even spreading of the coating on the surface of the tablet core.

(4) After conversion to fused film, greater than 0.5 N / m ^2, preferably a tensile strength greater than 3.5 N / m ^2. To protect the tablet during the next processing up to the administration of the tablet,
A moderately strong and tough coating is required.

(5) 50 ° C to 180 ° C, preferably 60 ° C to 100 ° C
Melting point in the range of ° C. With a relatively low melting point, less energy is required to convert the powder into the liquid phase, reducing the risk of damage to the tablet due to heating. The latter point is particularly important if the drug in the tablet core is susceptible to damage when its temperature rises significantly above room temperature.

Examples of materials that, alone or when combined with other materials, meet some or all of the five desirable properties listed above include polyamides, polyalkynes, waxes, oils, polyesters, sugar alcohols, It can be found in sugar, polyoxyethylene and ethylene vinyl acetate copolymers. Examples of suitable sugar alcohols are sorbitol and xylitol. Examples of suitable sugars are sucrose and lactose. A polyester having properties particularly suitable for the method of the present invention is polycaprolactone.

The materials set forth above can also be varied by blending other materials with them to improve their physical properties to more closely match the properties set forth above. One or more opacifiers, such as titanium dioxide and / or colorants, such as aluminum lakes or dyes, can also be provided in the formulation of the coating material.

The materials listed above belong to two classes: water-soluble materials (polyoxyethylene, sugars, alcohols) and slightly water-soluble or insoluble polymeric materials. A water-soluble material is generally desirable if the coating needs to dissolve rapidly following dosing, and a slightly water-soluble or insoluble heavy material if a delayed, controlled or regulated release of the drug is required. Coalescing materials are probably advantageous.

A particularly preferred sugar alcohol is xylitol, and a particularly preferred polymeric material is a polyester such as, for example, polycaprolactone. However, in both cases,
It is desirable to add small amounts of other substances to improve the physical properties of the material.

The present invention is used to apply controlled thickness coatings and to pharmaceuticals that contain a drug that is to be released immediately upon administration or to be controlled or regulated for release. Although it can be used, such control or regulation is achieved based on the properties of the coating and / or on the properties of the core. If the desired type of release is to be achieved based on the properties of the coating, it is desirable to leave a portion of the product uncoated or coated with a different material. In the case of a tablet having both sides at both ends connected by a cylindrical side wall, the uncoated or coated part with a different material may be the side of the tablet, one small part of both sides, or the side wall of the tablet, Anything is good.

As already made clear, the methods described above have the advantage that they can be performed continuously. Therefore, they can be used as part of a continuous process for producing coated pharmaceuticals, especially pharmaceutical tablets.

Thus, according to the present invention, a continuous process for producing a coated tablet, comprising the steps of continuously forming a pharmaceutical tablet core on a rotary press, and continuously coating the tablet core in a manner as defined above. Method is obtained.

According to the present invention, there is also provided an apparatus for carrying out the above-described method, comprising: a transport device; a device for feeding the core onto the transport device; And supplying at least one of the coating material, the transport device, and the core,
The potential of the coating material supplied to the area where the transfer device passes is made different from the potential of the core on the transfer device, so that the coating material is attracted to the exposed surface of the core and is exposed on the exposed surface. A charging device adapted to form a coating, the device comprising: a supply device for supplying a coating material in the form of a dry powder, further comprising: supplying the dry powder attracted to the core to the core. An apparatus is provided that includes an apparatus for processing the dry powder for conversion to a fixed fused film coating.

The apparatus may further include a rotary press, wherein the feeding device is operative to feed the core from the press onto the transport device.

The method and apparatus for electrostatic coating of a tablet core will now be described by way of example with reference to the accompanying drawings.

FIG. 1 is a schematic side view of an apparatus for coating tablets on one side, FIG. 2 is a block diagram of a continuous process for producing coated tablets using the apparatus of FIG. 1, FIG. FIG. 2 is a side view of a coated tablet.

The device shown in FIG.
It includes a conveyor belt 1 guided around a drive roller 3 driven by a motor 4 in the direction indicated by the arrow in the figure. Booth 5 around most of conveyor belt 1
Is provided.

A device for feeding tablet cores is provided at the upstream end (left end in FIG. 1) of the conveyor belt 1 outside the booth 5, but is not shown in this drawing. The type of device described above is not an integral part of the present invention. There is also provided a feeding device 6 for feeding the dry powder into the booth above the conveyor belt. In the example of the invention shown, an electrostatic powder gun using a single fixed corona electrode 7 attached to the end of a gun barrel 8 and connected to a voltage supply 9 comprises a feeding device. 6 are included. A mixture of powder and air is delivered from the Venturi powder feeder 10 to the gun barrel.

Electrodes 11, which are rectangular in plan and extend over the entire width of the conveyor belt 1 and part of its length, are suspended from the top of the booth. This electrode 11 is connected to a voltage supply 12. Another rectangular electrode 18 connected to earth
Supports it under the conveyor belt 1 in the region below the electrode 11. Conveyor belt 1
Made from a laminate of polyvinyl chloride and aluminum foil, the aluminum foil forms the outer layer of the belt, and the belt is connected to ground.

Above the downstream end of the conveyor belt, an infrared heater 13 and a vibrating plate 14 are provided.

During use of the device, the feeding device 6 feeds the pharmaceutical tablet core onto the upstream end of the belt 1 and places one side of the core on the belt, the other upward and passes along the conveyor. I do. The dry powder coated on the tablet core is
Blown into booth 5 by a spray gun that charges the powder to the appropriate potential (assuming that the powder is charged to a positive potential for this example). The powder sprayed from the gun enters the area between the electrode 11 maintained at a positive potential and the conveyor belt 1 and the electrode 18, both of which are grounded. The powder is thus directed away from the electrode 11 and downwards with respect to the conveyor belt 1 and the electrode 18. Thus, a powder coating is placed on the conveyor belt and the tablet cores on the conveyor belt.

The tablet core is then passed under an infrared heater 13 which heats the coating of the powder on the tablet enough to melt the coating and form a film coating on the upper surface of the tablet core. As the tablets are conveyed past the heater 13, they are contacted with a vibrating plate 14 which equalizes the coating.

To apply a coating (if it is desired) on the other side of the tablet core, the powder is reversed onto another conveyor device similar to that shown in FIG. The process described above in connection with is repeated. Devices for transferring tablets from one conveyor to another and turning them over during the transfer are already known (see, for example, GB-1 075 404 GB).

Referring now to FIG. It should be appreciated that the just described equipment and dimensions provide for continuous production of coated tablets. Tablet cores produced, for example, by a high speed rotary press are fed directly to the apparatus of FIG. 1, where their upper surfaces are coated with a charged dry powder. The dry powder is then melted by heating and the partially coated dry powder is allowed to cool, this time with another device of the type shown in FIG. 1 with their uncoated surfaces on top. Is sent to Those uncoated surfaces are
Coated with a charged dry powder, the dry powder coating is melted by heating, the coated tablets are allowed to cool, and then fed to a suitable packaging machine. The above process can operate continuously.

FIG. 3 shows a tablet having an upper surface 15, a lower surface 16 and a cylindrical side surface 17. In the first coating stage, one of the faces, for example face 15, is completely coated, and the side walls 17 receive some but not a complete powder coating. In the second coating stage, the other side 16 is completely coated and the remaining coating on the side wall 17 is applied.

────────────────────────────────────────────────── ─── Continued on the front page (56) References JP-B-38-17688 (JP, B1) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61J 3/06 A61K 9/28 A61K 9 / 50

Claims (28)

(57) [Claims] A step of feeding a pharmaceutical tablet core onto a transport device; a step of supplying a coating material to an area through which the core passes as the core is transported over the transport device; Maintaining the core at a different potential and transporting the core through the area on the transport device, whereby the coating material is attracted to the exposed surface of the core to form a coating on the exposed surface A method of coating a pharmaceutical tablet core with a coating material, comprising: using a dry powder as the coating material;
After the dry powder is attracted to the exposed surface of the core to form a coating on the exposed surface, the dry powder is treated such that the dry powder is converted to a fused film coating adhered to the core. A method comprising: 2. The method according to claim 1, wherein
A method whereby the method is performed as a continuous process. 3. The method according to claim 1, wherein the surface of the core that has been in contact with the transfer device in the transfer step is exposed, and the fused film coating of the core is transferred. Contacting the device, feeding the tablet core onto the transport device, supplying the dry powder coated on the core to an area where the transport device passes, the transport device or the core, or the like. Maintaining both at a different potential than the dry powder and transporting the core through the area on the transport device such that the dry powder is attracted to the exposed surface of the core And treating this dry powder coating such that the newly attracted powder is converted to a fused film coating affixed to the core. Method to include as a continuation step. 4. The method according to claim 3, wherein
The method wherein the transport device used during the second coating stage is different from the transport device used during the first coating stage. 5. The method according to claim 1, wherein said transport device comprises a conveyor belt. 6. A method according to any one of claims 1 to 5, wherein the coating is further added so as to equalize the depth of the coating on the surface of the core. A method comprising applying a mechanical treatment. 7. The method according to claim 6, wherein
A method wherein the equalizing step is performed by passing the core under a vibrating plate or rotating roller, the plate or roller contacting and equalizing the coating on the core. 8. The method according to claim 6, wherein:
The method wherein the equalization step is performed by passing the core under a jet of air. 9. The method according to claim 1, wherein the dry powder coating is converted to a fused film by heating. 10. The method according to any one of claims 1 to 9, wherein the powder is charged. 11. The method according to claim 10, wherein the powder is charged as it is supplied to the area through which the transport device passes. 12. The method according to claim 10, wherein charging is performed using a corona charging device. 13. The method according to any one of claims 1 to 12, wherein one or more sets of electrodes maintained at a selected potential are arranged above said transport device. A method provided in the area where the powder is supplied. 14. The method according to any one of claims 1 to 13, wherein the powder is 1 μm
A method having a particle size in the range from to 1000 μm. 15. The method according to claim 1, wherein the powder has a relatively high resistivity in the range of 10 ⁶ to 10 ²⁴ Ωm. . 16. The method according to claim 1, wherein said powder has a viscosity of less than 500 Pas when in the liquid phase. 17. The method according to any one of claims 1 to 16, wherein the powder has a tensile strength of more than 0.5 N / m ² after returning to the solid phase. How to have. 18. The method according to any one of claims 1 to 17, wherein the powder has a melting point in the range from 50 ° C to 180 ° C. 19. The method according to claim 18, wherein said powder has a melting point in the range from 60 ° C. to 100 ° C. 20. The method according to any one of claims 1 to 19, wherein said dry powder is completely or substantially polyamide, polyalkyne, wax, oil, polyester, polyoxyethylene. A process comprising one or more materials in the group comprising: a sugar, a sugar alcohol, and an ethylene vinyl acetate copolymer. 21. The method of claim 20, wherein said dry powder consists entirely or substantially of xylitol. 22. The method according to claim 20, wherein said dry powder consists entirely or substantially of polycaprolactone. 23. The method according to any one of claims 1 to 22, wherein the tablet core is added to increase the electrical conductivity of the tablet core before applying the powder. How to handle. 24. The method according to claim 23, wherein:
The method wherein the treatment comprises wetting the exterior of the tablet core. 25. A method for continuously producing coated tablets, comprising the steps of: forming a continuous pharmaceutical tablet core on a rotary press; and any one of claims 1 to 24. Coating the tablet core continuously according to the method of one of the preceding paragraphs. 26. An apparatus for carrying out the method according to any one of claims 1 to 24, comprising: a transport device; and feeding the core onto the transport device. A coating device, a supply device for supplying a coating material to an area where the transfer device passes, and charging at least one of the coating material, the transfer device, and the core so that the transfer device passes therethrough. The potential of the coating material supplied to the area to be applied is different from the potential of the core on the transport device, such that the coating material is attracted to the exposed surface of the core to form a coating on the exposed surface. A charging device, comprising: a supply device for supplying a coating material in the form of a dry powder; and further comprising a dry powder attracted to said core. To convert the anchored fusion film coating on the core, device characterized in that it comprises a device for processing the dried powder. 27. The apparatus according to claim 26, further comprising a rotary press, wherein said supply device is operable to supply said core from said rotary press onto said transport device. 28. Apparatus according to claim 26 or claim 27, wherein the transport device comprises an inclined stationary surface.